Incessant cycles of dystrophic myofiber degeneration and regeneration result in ubiquitous centrally-nucleated fibers in skeletal muscles of X-chromosome-linked muscular dystrophy (mdx) mouse

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Duchenne muscular dystrophy (DMD) is an X-linked recessive, degenerative disorder and is the most prevalent, devastating and fatal pediatric neuromuscular disorder in the world. DMD is primarily caused by loss-of-function mutations in the dystrophin gene that result in either partial and dysfunctional domains in dystrophin protein or complete absence of it, leading to contractioninduced necrosis of skeletal muscle fibers and eventual replacement with adipose and connective tissue. Ultimately, rapid and subjugating progression of myofiber degeneration and necrosis, along with gradual attenuation and failure of regenerative capacity, rather than failure of muscle development, result in the crippling phenotype of DMD. The X-chromosome-linked muscular dystrophy (mdx) mouse is genetically homologous to human DMD but exhibits a milder phenotype and evades severe end-stage histopathology. Histopathologic analysis revealed that skeletal muscles of mdx mice exhibit drastically elevated levels of centrally-nucleated myofibers, similar to humans with DMD, as a result of incessant cycles of dystrophic myofiber degeneration and regeneration.